Skip to main content
AAN.com

Abstract

Parkinson disease (PD) is the second most common neurodegenerative disease, and the most common synucleinopathy, as alpha-synuclein (α-syn), a prion-like protein, plays an important pathophysiologic role in its onset and progression. Although neuropathologic changes begin many years before the onset of motor manifestations, diagnosis still relies on the identification of the motor symptoms, which hinders to formulate an early diagnosis. Because α-syn misfolding and aggregation precede clinical manifestations, the possibility to identify these phenomena in patients with PD would allow us to recognize the disease at the earliest, premotor phases, as a consequence of the transition from a clinical to a molecular diagnosis. Seed amplification assays (SAAs) are a group of techniques that currently support the diagnosis of prion subacute encephalopathies, namely Creutzfeldt-Jakob disease. These techniques enable the detection of minimal amounts of prions in CSF and other matrices of affected patients. Recently, SAAs have been successfully applied to detect misfolded alpha-synuclein (α-syn) in CSF, olfactory mucosa, submandibular gland biopsies, skin, and saliva of patients with Parkinson disease (PD) and other synucleinopathies. In these categories, they can differentiate PD and dementia with Lewy bodies (DLBs) from control subjects, even in the prodromal stages of the disease. In differential diagnosis, SAAs satisfactorily differentiated PD, DLB, and multiple system atrophy (MSA) from nonsynucleinopathy parkinsonisms. The kinetic analysis of the SAA fluorescence profiles allowed the identification of synucleinopathy-dependent α-syn fibrils conformations, commonly referred to as strains, which have demonstrated diagnostic potential in differentiating among synucleinopathies, especially between Lewy body diseases (LBDs) (PD and DLB) and MSA. In front of these highly promising data, which make the α-syn seeding activity detected by SAAs as the most promising diagnostic biomarker for synucleinopathies, there are still preanalytical and analytical issues, mostly related to the assay standardization, which need to be solved. In this review, we discuss the key findings supporting the clinical application of α-syn SAAs to identify PD and other synucleinopathies, the unmet needs, and future perspectives.

Get full access to this article

View all available purchase options and get full access to this article.

References

1.
Soto C, Pritzkow S. Protein misfolding, aggregation, and conformational strains in neurodegenerative diseases. Nat Neurosci. 2018;21(10):1332-1340.
2.
Koga S, Sekiya H, Kondru N, Ross OA, Dickson DW. Neuropathology and molecular diagnosis of Synucleinopathies. Mol Neurodegeneration. 2021;16(1):83.
3.
Braak H, Del Tredici K. Neuropathological staging of brain pathology in sporadic Parkinson's disease: separating the wheat from the chaff. J Parkinsons Dis. 2017;7(s1):S71–S85.
4.
Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson's disease: MDS-PD clinical diagnostic criteria. Mov Disord. 2015;30(12):1591-1601.
5.
Fereshtehnejad S-M, Montplaisir JY, Pelletier A, Gagnon J-F, Berg D, Postuma RB. Validation of the MDS research criteria for prodromal Parkinson's disease: longitudinal assessment in a REM sleep behavior disorder (RBD) cohort. Mov Disord official J Mov Disord Soc. 2017;32(6):865-873.
6.
Heinzel S, Berg D, Gasser T, Chen H, Yao C, Postuma RB, MDS Task Force on the Definition of Parkinson's Disease. Update of the MDS research criteria for prodromal Parkinson's disease. Mov Disord. 2019;34(10):1464-1470.
7.
Gaetani L, Paolini Paoletti F, Bellomo G, et al. CSF and blood biomarkers in neuroinflammatory and neurodegenerative diseases: implications for treatment. Trends Pharmacol Sci. 2020;41(12):1023-1037.
8.
Jack CR, Bennett DA, Blennow K, et al., Contributors. NIA-AA Research Framework: toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018;14(4):535-562.
9.
Barba L, Paolini Paoletti F, Bellomo G, et al. Alpha and beta synucleins: from pathophysiology to clinical application as biomarkers. Mov Disord official J Mov Disord Soc. 2022;37(4):669-683.
10.
Majbour NK, Vaikath NN, van Dijk KD, et al. Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson's disease. Mol Neurodegeneration. 2016;11:7.
11.
Manix M, Kalakoti P, Henry M, et al. Creutzfeldt-Jakob disease: updated diagnostic criteria, treatment algorithm, and the utility of brain biopsy. Neurosurg Focus. 2015;39(5):E2.
12.
Orrú CD, Groveman BR, Foutz A, et al. Ring trial of 2nd generation RT‐QuIC diagnostic tests for sporadic CJD. Ann Clin Transl Neurol. 2020;7(11):2262-2271.
13.
Hermann P, Laux M, Glatzel M, et al. Validation and utilization of amended diagnostic criteria in Creutzfeldt-Jakob disease surveillance. Neurology. 2018;91(4):e331–e338.
14.
Giaccone G, Moda F. PMCA applications for prion detection in peripheral tissues of patients with variant Creutzfeldt-Jakob disease. Biomolecules. 2020;10(3):405.
15.
Salvadores N, Shahnawaz M, Scarpini E, Tagliavini F, Soto C. Detection of misfolded Aβ oligomers for sensitive biochemical diagnosis of Alzheimer's disease. Cell Rep. 2014;7(1):261-268.
16.
Shahnawaz M, Tokuda T, Waragai M, et al. Development of a biochemical diagnosis of Parkinson disease by detection of α-synuclein misfolded aggregates in cerebrospinal fluid. JAMA Neurol. 2017;74(2):163-172.
17.
Fairfoul G, McGuire LI, Pal S, et al. Alpha-synuclein RT-QuIC in the CSF of patients with alpha-synucleinopathies. Ann Clin Translational Neurol. 2016;3(10):812-818.
18.
Groveman BR, Orrù CD, Hughson AG, et al. Rapid and ultra-sensitive quantitation of disease-associated α-synuclein seeds in brain and cerebrospinal fluid by αSyn RT-QuIC. Acta Neuropathologica Commun. 2018;6(1):7.
19.
Kang UJ, Boehme AK, Fairfoul G, et al. Comparative study of cerebrospinal fluid α-synuclein seeding aggregation assays for diagnosis of Parkinson's disease. Mov Disord official J Mov Disord Soc. 2019;34(4):536-544.
20.
Ferreira NdC, Caughey B. Proteopathic seed amplification assays for neurodegenerative disorders. Clin Lab Med. 2020;40(3):257-270.
21.
Garrido A, Fairfoul G, Tolosa ES, Martí MJ, Green A, Barcelona LRRK2 Study Group. α‐synuclein RT‐QuIC in cerebrospinal fluid of LRRK2‐linked Parkinson's disease. Ann Clin Transl Neurol. 2019;6:1024-1032.
22.
Rossi M, Candelise N, Baiardi S, et al. Ultrasensitive RT-QuIC assay with high sensitivity and specificity for Lewy body-associated synucleinopathies. Acta Neuropathologica. 2020;140(1):49-62.
23.
Shahnawaz M, Mukherjee A, Pritzkow S, et al. Discriminating α-synuclein strains in Parkinson's disease and multiple system atrophy. Nature. 2020;578(7794):273-277.
24.
van Rumund A, Green AJE, Fairfoul G, Esselink RAJ, Bloem BR, Verbeek MM. α‐Synuclein real‐time quaking‐induced conversion in the cerebrospinal fluid of uncertain cases of parkinsonism. Ann Neurol. 2019;85(5):777-781.
25.
Poggiolini I, Gupta V, Lawton M, et al. Diagnostic value of cerebrospinal fluid alpha-synuclein seed quantification in synucleinopathies. Brain. 2022;145(2):584-595.
26.
Visanji NP, Mollenhauer B, Beach TG, et al., Systemic Synuclein Sampling Study S4. The systemic synuclein sampling study: toward a biomarker for Parkinson's disease. Biomarkers Med. 2017;11(4):359-368.
27.
Manne S, Kondru N, Jin H, et al. Blinded RT-QuIC analysis of α-synuclein biomarker in skin tissue from Parkinson's disease patients. Mov Disord official J Mov Disord Soc. 2020;35(12):2230-2239.
28.
Brozzetti L, Sacchetto L, Cecchini MP, et al. Neurodegeneration-associated proteins in human olfactory neurons collected by nasal brushing. Front Neurosci. 2020;14:145.
29.
Rey NL, George S, Steiner JA, et al. Spread of aggregates after olfactory bulb injection of α-synuclein fibrils is associated with early neuronal loss and is reduced long term. Acta Neuropathol. 2018;135(1):65-83.
30.
De Luca CMG, Elia AE, Portaleone SM, et al. Efficient RT-QuIC seeding activity for α-synuclein in olfactory mucosa samples of patients with Parkinson's disease and multiple system atrophy. Transl Neurodegener. 2019;8:24.
31.
Donadio V, Wang Z, Incensi A, et al. In vivo diagnosis of synucleinopathies: a comparative study of skin biopsy and RT-QuIC. Neurology. 2021;96(20):e2513-e2524.
32.
Mammana A, Baiardi S, Quadalti C, et al. RT-QuIC detection of pathological α-synuclein in skin punches of patients with Lewy body disease. Mov Disord official J Mov Disord Soc. 2021;36(9):2173-2177.
33.
Wang Z, Becker K, Donadio V, et al. Skin α-synuclein aggregation seeding activity as a novel biomarker for Parkinson disease. JAMA Neurol. 2020;78:30.
34.
Kuzkina A, Bargar C, Schmitt D, et al. Diagnostic value of skin RT-QuIC in Parkinson's disease: a two-laboratory study. Npj Parkinsons Dis. 2021;7:99.
35.
Bargar C, De Luca CMG, Devigili G, et al. Discrimination of MSA-P and MSA-C by RT-QuIC analysis of olfactory mucosa: the first assessment of assay reproducibility between two specialized laboratories. Mol Neurodegeneration. 2021;16(1):82.
36.
Perra D, Bongianni M, Novi G, et al. Alpha-synuclein seeds in olfactory mucosa and cerebrospinal fluid of patients with dementia with Lewy bodies. Brain Commun. 2021;3(2):fcab045.
37.
Manne S, Kondru N, Jin H, et al. α-Synuclein real-time quaking-induced conversion in the submandibular glands of Parkinson's disease patients. Mov Disord. 2020;35(2):268-278.
38.
Luan M, Sun Y, Chen J, et al. Diagnostic value of salivary real-time quaking-induced conversion in Parkinson's disease and multiple system Atrophy. Mov Disord. 2022;37(5):1059-1063.
39.
Iranzo A, Molinuevo JL, Santamaría J, et al. Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study. Lancet Neurol. 2006;5(7):572-577.
40.
Iranzo A, Fernández-Arcos A, Tolosa E, et al. Neurodegenerative disorder risk in idiopathic REM sleep behavior disorder: study in 174 patients. PLoS One. 2014;9(2):e89741.
41.
Postuma RB, Gagnon J-F, Bertrand J-A, Génier Marchand D, Montplaisir JY. Parkinson risk in idiopathic REM sleep behavior disorder: preparing for neuroprotective trials. Neurology .2015;84(11):1104-1113.
42.
Iranzo A, Fairfoul G, Ayudhaya ACN, et al. Detection of α-synuclein in CSF by RT-QuIC in patients with isolated rapid-eye-movement sleep behaviour disorder: a longitudinal observational study. Lancet Neurol. 2021;20(3):203-212.
43.
Stefani A, Iranzo A, Holzknecht E, et al., SINBAR Sleep Innsbruck Barcelona Group. Alpha-synuclein seeds in olfactory mucosa of patients with isolated REM sleep behaviour disorder. Brain. 2021;144(4):1118-1126.
44.
Quadalti C, Calandra-Buonaura G, Baiardi S, et al. Neurofilament light chain and α-synuclein RT-QuIC as differential diagnostic biomarkers in parkinsonisms and related syndromes. Npj Parkinsons Dis. 2021;7:93.
45.
Van der Perren A, Gelders G, Fenyi A, et al. The structural differences between patient-derived α-synuclein strains dictate characteristics of Parkinson's disease, multiple system atrophy and dementia with Lewy bodies. Acta Neuropathol. 2020;139(6):977-1000.
46.
Peng C, Gathagan RJ, Covell DJ, et al. Cellular milieu imparts distinct pathological α-synuclein strains in α-synucleinopathies. Nature. 2018;557(7706):558-563.
47.
Ayers JI, Lee J, Monteiro O, et al. Different α-synuclein prion strains cause dementia with Lewy bodies and multiple system atrophy. Proc Natl Acad Sci United States America. 2022;119(6):e2113489119.
48.
Strohäker T, Jung BC, Liou S-H, et al. Structural heterogeneity of α-synuclein fibrils amplified from patient brain extracts. Nat Commun. 2019;10(1):5535.
49.
Schweighauser M, Shi Y, Tarutani A, et al. Structures of α-synuclein filaments from multiple system atrophy. Nature. 2020;585(7825):464-469.
50.
Bellomo G, Paciotti S, Gatticchi L, et al. Seed amplification assays for diagnosing synucleinopathies: the issue of influencing factors. Front Biosci (Landmark Ed). 2021;26(11):1075-1088.
51.
Russo MJ, Orru CD, Concha-Marambio L, et al. High diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early Parkinson's disease. Acta Neuropathologica Commun. 2021;9(1):179.
52.
Bargar C, Wang W, Gunzler SA, et al. Streamlined alpha-synuclein RT-QuIC assay for various biospecimens in Parkinson's disease and dementia with Lewy bodies. Acta Neuropathologica Commun. 2021;9(1):62.
53.
Spires-Jones TL, Attems J, Thal DR. Interactions of pathological proteins in neurodegenerative diseases. Acta Neuropathol. 2017;134(2):187-205.
54.
Bellomo G, Paciotti S, Gatticchi L, Parnetti L. The vicious cycle between α-synuclein aggregation and autophagic-lysosomal dysfunction. Mov Disord. 2020;35(1):34-44.
55.
Irwin DJ, Hurtig HI. The contribution of tau, amyloid-beta and alpha-synuclein pathology to dementia in Lewy body disorders. J Alzheimers Dis Parkinsonism. 2018;8(4):444.
56.
Bellomo G, Paolini Paoletti F, Chipi E, et al. A/T/(N) profile in cerebrospinal fluid of Parkinson's disease with/without cognitive impairment and dementia with Lewy bodies. Diagnostics (Basel). 2020;10(12):E1015.
57.
Brockmann K, Quadalti C, Lerche S, et al. Association between CSF alpha-synuclein seeding activity and genetic status in Parkinson's disease and dementia with Lewy bodies. Acta Neuropathologica Commun. 2021;9(1):175.
58.
Kalia LV, Lang AE, Hazrati L-N, et al. Clinical correlations with Lewy body pathology in LRRK2-related Parkinson disease. JAMA Neurol. 2015;72(1):100-105.
59.
Orrù CD, Ma TC, Hughson AG, et al. A rapid α‐synuclein seed assay of Parkinson's disease CSF panel shows high diagnostic accuracy. Ann Clin Transl Neurol. 2021;8(2):374-384.
60.
Bongianni M, Ladogana A, Capaldi S, et al. α-Synuclein RT-QuIC assay in cerebrospinal fluid of patients with dementia with Lewy bodies. Ann Clin Transl Neurol. 2019;6(10):2120-2126.
61.
Rossi M, Baiardi S, Teunissen CE, et al. Diagnostic value of the CSF α-synuclein real-time quaking-induced conversion assay at the prodromal MCI stage of dementia with Lewy bodies. Neurology. 2021;97(9):e930-e940.
Letters to the Editor

Information & Authors

Information

Published In

Neurology®
Volume 99Number 5August 2, 2022
Pages: 195-205
PubMed: 35914941

Publication History

Received: January 13, 2022
Accepted: May 10, 2022
Published online: June 3, 2022
Published in print: August 2, 2022

Permissions

Request permissions for this article.

Disclosure

The authors report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.

Study Funding

The authors report no targeted funding.

Authors

Affiliations & Disclosures

From the Section of Neurology, Lab of Clinical Neurochemistry, Department of Medicine and Surgery, University of Perugia, Italy (G.B., F.P.P., L.G., L.P.); and Unit of Neurology 5 and Neuropathology (C.M.G.D.L., F.M.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Chiara Maria Giulia De Luca, MSc https://orcid.org/0000-0002-6233-8272
From the Section of Neurology, Lab of Clinical Neurochemistry, Department of Medicine and Surgery, University of Perugia, Italy (G.B., F.P.P., L.G., L.P.); and Unit of Neurology 5 and Neuropathology (C.M.G.D.L., F.M.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Federico Paolini Paoletti, MD, PhD https://orcid.org/0000-0001-9623-1900
From the Section of Neurology, Lab of Clinical Neurochemistry, Department of Medicine and Surgery, University of Perugia, Italy (G.B., F.P.P., L.G., L.P.); and Unit of Neurology 5 and Neuropathology (C.M.G.D.L., F.M.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Lorenzo Gaetani, MD, PhD https://orcid.org/0000-0003-3967-8954
From the Section of Neurology, Lab of Clinical Neurochemistry, Department of Medicine and Surgery, University of Perugia, Italy (G.B., F.P.P., L.G., L.P.); and Unit of Neurology 5 and Neuropathology (C.M.G.D.L., F.M.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
From the Section of Neurology, Lab of Clinical Neurochemistry, Department of Medicine and Surgery, University of Perugia, Italy (G.B., F.P.P., L.G., L.P.); and Unit of Neurology 5 and Neuropathology (C.M.G.D.L., F.M.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Lucilla Parnetti, MD, PhD https://orcid.org/0000-0001-5722-3967
From the Section of Neurology, Lab of Clinical Neurochemistry, Department of Medicine and Surgery, University of Perugia, Italy (G.B., F.P.P., L.G., L.P.); and Unit of Neurology 5 and Neuropathology (C.M.G.D.L., F.M.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Correspondence Dr. Parnetti [email protected]
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editor was Peter Hedera, MD, PhD.

Metrics & Citations

Metrics

Citations

Download Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.

Cited By
  1. Fluid Biomarkers for Trial Enrichment and Effect Monitoring in Disease-Modifying Treatments for Parkinson Disease, Neurology, 102, 5, (2024)./doi/10.1212/WNL.0000000000209194
    Abstract
  2. On gaps of clinical diagnosis of dementia subtypes: A study of Alzheimer’s disease and Lewy body disease, Frontiers in Aging Neuroscience, 15, (2023).https://doi.org/10.3389/fnagi.2023.1149036
    Crossref
  3. Proposal for a Biologic Staging System of Parkinson’s Disease, Journal of Parkinson's Disease, 13, 3, (297-309), (2023).https://doi.org/10.3233/JPD-225111
    Crossref
  4. Validation Study of the MDS Criteria for the Diagnosis of Multiple System Atrophy in the Mayo Clinic Brain Bank, Neurology, 101, 24, (e2460-e2471), (2023)./doi/10.1212/WNL.0000000000207905
    Abstract
  5. Advances in Diagnosis and Prognosis of Parkinson Disease, Neurology, 101, 14, (595-596), (2023)./doi/10.1212/WNL.0000000000207724
    Abstract
  6. CSF Synaptic Biomarkers in AT(N)-Based Subgroups of Lewy Body Disease, Neurology, 101, 1, (e50-e62), (2023)./doi/10.1212/WNL.0000000000207371
    Abstract
  7. On the Track of α-Synuclein in the Body, Neurology, 100, 15, (691-692), (2023)./doi/10.1212/WNL.0000000000206881
    Abstract
  8. Cerebrospinal fluid lipoproteins inhibit α-synuclein aggregation by interacting with oligomeric species in seed amplification assays, Molecular Neurodegeneration, 18, 1, (2023).https://doi.org/10.1186/s13024-023-00613-8
    Crossref
  9. How should we be using biomarkers in trials of disease modification in Parkinson’s disease?, Brain, 146, 12, (4845-4869), (2023).https://doi.org/10.1093/brain/awad265
    Crossref
  10. Reducing the number of patients needed in disease modifying trials for parkinsonian disorders, Brain, 146, 8, (3101-3102), (2023).https://doi.org/10.1093/brain/awad179
    Crossref
  11. See more
Loading...

View Options

Get Access

Login options

Check if you have access through your login credentials or your institution to get full access on this article.

Personal login Institutional Login
Purchase Options

Purchase this article to get full access to it.

Purchase Access, $39 for 24hr of access

View options

Full Text

View Full Text

Full Text HTML

View Full Text HTML

Media

Figures

Other

Tables

Share

Share

Share article link

Share